Compared with conventional photon (X- and γ-rays) radiotherapy, a main advantage of ion beam radiotherapy is that doses can be precisely positioned in a Bragg peak, and thus tumor cells can be efficiently killed while protecting normal tissues. Furthermore, heavy ions such as carbon ions also have characteristics such as high relative biological effectiveness (RBE) and small lateral scattering. For treatment of target volumes having relatively fixed positions and shapes, for example, head and neck tumors, an irradiation with sufficiently high accuracy can be ensured due to right positioning and immobilization for patients before the irradiation. However, tumors located in the thoracic and abdominal regions, including lung cancer, liver cancer, prostate cancer, and the like, are moved along with respiratory motions of the patients. In a therapy course, interplays between target motion and dynamic beam delivery can cause serious distortion of dose distributions, thus resulting in cold and hot spots of local doses in the target volume and limiting the normal tissue sparing potential of ion beam radiotherapy. In order to take full advantage of the ion beam therapies, and further improve the efficacy of the ion beam therapies and reduce radiation injury to the healthy tissues, it is quite necessary to carry out some research aiming at moving target irradiation techniques in the ion beam therapies, which is also the important development direction and trend in the research area of the ion beam therapies in the word.
Existing respiratory gating and breath-hold techniques have been widely used in clinical treatment to reduce or eliminate the unfavorable impact of the target motion. Recently, a new respiratory motion compensation method, in which conventional respiratory gating and breath-hold (BH) techniques and a personalized audio-visual biofeedback system are combined, was proposed by Park et al. (Y. K. Park, et al. Quasi-breath-hold technique using personalized audio-visual biofeedback for respiratory motion management in radiotherapy. Medical Physics. 2011, 38: 3114-3124). In this technique, subjects repeat physiological actions of respiratory breath-hold under the guidance of the audio-visual biofeedback system, so that respiratory frequencies and amplitudes of the subjects can become uniform, and then the target residual motions within the gating windows can be effectively reduced. Furthermore, compared with simple respiratory breath-hold techniques, this technique can reduce the complexity of doctor-patient cooperation during the treatment course. However, application objects of this technique are based on the conventional photon radiotherapy under a continuous beam delivery mode provided by a linear accelerator.
At present, there are two types of accelerator system in the ion beam radiotherapy, i.e. cyclotron and synchrotron. Cyclotron provides a continuous beam delivery mode similar to the linear accelerator, and thus it is relatively simple for optimizing respiratory-gated irradiation parameters, the target motion compensation method proposed by Park et al. can be directly translated to this setting. For ion beam acceleration systems on the basis of synchrotron, pulsed ion beams are provided, and the duration of magnet excitation cycles thereof is close to human's respiratory cycles. Usually the synchrotron uses a slow beam extraction mode, and the beams can be extracted only in a partial time of the magnet excitation cycles. An entire magnet excitation cycle includes an acceleration stage, a flat-top stage (beam extraction) and a deceleration stage. In a gated irradiation, the beams can be extracted only in a period of time that the gated-on state coincides with the flat-top stage. Thus, the premise of implementing an efficient respiratory-gated irradiation relies on the optimization of the synchronization between the magnet excitation cycle and each patient's respiratory cycle. A slight difference between the above two can result in decreased efficiency of the respiratory-gated irradiation.
Tsunashima et al. have investigated the efficiency of respiratory-gated irradiation using protons on the basis of a pulsed synchrotron (Y. Tsunashima, et al. Efficiency of respiratory-gated delivery of synchrotron-based pulsed proton irradiation. Physics in Medicine and Biology. 2008, 53: 1947-1959). In their work, a realistic simulation of the interaction of various accelerator operation parameters and patient respiratory parameters was conducted to determine optimal parameter settings, so as to improve the efficiency of the respiratory-gated proton beam irradiation. They found that the average beam delivery time was tripled by using a fixed magnet excitation cycle pattern, and the treatment time was only doubled by using a variable magnet excitation cycle pattern. In another study, they also found that the variable magnet excitation cycle method can improve the accuracy of the irradiation at the same time (Y. Tsunashima, et al. The precision of respiratory-gated delivery of synchrotron-based pulsed beam proton therapy. Physics in Medicine and Biology. 2010, 55: 7633-7647). Although this method can effectively improve the efficacy of the therapy, an implementation of a treatment plan often needs a series of pulsed beams, and each of the magnet excitation cycles must be set prior to the start of delivery for each beam, and the cycle of the next respiration of the patient needs to be predicted after the last beam spill but before the start of irradiation with the next spill. Although the method improves respiratory efficiency with respect to the fixed magnet excitation cycle mode, the complex operation process can easily cause errors, and thus the entire irradiation time is still doubled.